rs773825578

Variant names:

• chr17-732711-G-C
• rs773825578
• NM_024792.3:c.64G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-732711-G-C
• chr17-732711-G-A
• chr17-732711-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024792.3(TLCD3A):​c.64G>C​(p.Ala22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,440,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: TLCD3A NM_024792.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0260
• Publications: 0 publications found

Genes affected

TLCD3A (HGNC:29646): (TLC domain containing 3A) The protein encoded by this gene is a membrane-associated protein that promotes lung carcinogenesis. The encoded protein may be involved in amino acid transport and glutathione metabolism since it can interact with a solute carrier family member (SLC3A2) and an isoform of gamma-glutamyltranspeptidase-like 3. An alternatively spliced variant encoding a protein that lacks a 32 aa internal segment showed the opposite effect, inhibiting lung cancer cell growth. Knockdown of this gene also inhibited lung carcinogenesis and tumor cell growth. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052179307).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024792.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD3A	NM_024792.3	MANE Select	c.64G>C	p.Ala22Pro	missense	Exon 1 of 5	NP_079068.1	Q8TBR7-2
	TLCD3A	NM_001318006.2		c.64G>C	p.Ala22Pro	missense	Exon 1 of 4	NP_001304935.1	Q8TBR7-1
	TLCD3A	NM_001318007.2		c.64G>C	p.Ala22Pro	missense	Exon 1 of 4	NP_001304936.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD3A	ENST00000308278.13	TSL:1 MANE Select	c.64G>C	p.Ala22Pro	missense	Exon 1 of 5	ENSP00000312017.7	Q8TBR7-2
	TLCD3A	ENST00000301324.8	TSL:1	c.64G>C	p.Ala22Pro	missense	Exon 1 of 4	ENSP00000301324.8	Q8TBR7-1
	TLCD3A	ENST00000572018.5	TSL:3	c.64G>C	p.Ala22Pro	missense	Exon 1 of 3	ENSP00000460150.1	I3L336

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151846 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000405 AC: 3 AN: 74102 AF XY: 0.0000235

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000792

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000473 AC: 61 AN: 1288952 Hom.: 1 Cov.: 31 AF XY: 0.0000410 AC XY: 26 AN XY: 634692

African (AFR) AF: 0.00 AC: 0 AN: 26124

American (AMR) AF: 0.00 AC: 0 AN: 24908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22314

East Asian (EAS) AF: 0.00202 AC: 55 AN: 27190

South Asian (SAS) AF: 0.0000576 AC: 4 AN: 69488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3882

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1030132

Other (OTH) AF: 0.0000379 AC: 2 AN: 52778

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151952 Hom.: 0 Cov.: 33 AF XY: 0.0000943 AC XY: 7 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41530

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5130

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67892

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000315 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.026
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Benign	0.22	T
Sift4G	Benign	0.22	T
Polyphen		0.38	B
Vest4		0.26
MutPred		0.57		Loss of helix (P = 0.028)
MVP		0.11
MPC		0.44
ClinPred		0.040	T
GERP RS		0.54
PromoterAI		0.015	Neutral
Varity_R		0.16
gMVP		0.59
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs773825578; hg19: chr17-635951;